Bone response to biomimetic implants delivering BMP-2 and VEGF: an immunohistochemical study.
This animal study evaluated bone healing around titanium implant surfaces biomimetically coated with bone morphogenic protein-2 (BMP-2) and/or vascular endothelial growth factor (VEGF) by examining bone matrix proteins and mineralisation. Five different implant surfaces were established: acid-etched surface (AE), biomimetic calcium phosphate surface (CAP), BMP-2 loaded CAP surface, VEGF loaded CAP surface and dual BMP-2 + VEGF loaded CAP surface. The implants were inserted into calvariae of adult domestic pigs. For the comparison of osteoconductive capacity of each surface, bone mineral density and expression of bone matrix proteins (collagen I, BMP-2/4, osteocalcin and osteopontin) inside defined chambers around the implant were assessed using light microscopy and microradiography and immunohistochemical analysis at 1, 2 and 4 weeks. In the both groups delivering BMP-2, the bone mineral density was significantly enhanced after 2 weeks and the highest value was measured for the group BMP + VEGF. In the group VEGF, collagen I and BMP-2/4 expressions were significantly up-regulated at the first and second weeks. The percentage of BMP-2/4 positive cells in the group BMP + VEGF was significantly enhanced compared with the groups AE and CAP at the second week. Although the highest osteocalcin and osteopontin expression values were observed for the group BMP + VEGF after 2 weeks, no statistically significant difference in osteocalcin and osteopontin expressions was found between all groups at any time. It was concluded that combined delivery of BMP-2 and VEGF favoured bone mineralisation and expression of important bone matrix proteins that might explain synergistic interaction between both growth factors.


Validity of Cardiovascular Data From Electronic Sources: The Multi-Ethnic Study of Atherosclerosis and HealthLNK.
Understanding the validity of data from electronic data research networks is critical to national research initiatives and learning healthcare systems for cardiovascular care. Our goal was to evaluate the degree of agreement of electronic data research networks in comparison with data collected by standardized research approaches in a cohort study. We linked individual-level data from MESA (Multi-Ethnic Study of Atherosclerosis), a community-based cohort, with HealthLNK, a 2006 to 2012 database of electronic health records from 6 Chicago health systems. To evaluate the correlation and agreement of blood pressure in HealthLNK in comparison with in-person MESA examinations, and body mass index in HealthLNK in comparison with MESA, we used Pearson correlation coefficients and Bland-Altman plots. Using diagnoses in MESA as the criterion standard, we calculated the performance of HealthLNK for hypertension, obesity, and diabetes mellitus diagnosis by using International Classification of Diseases, Ninth Revision codes and clinical data. We also identified potential myocardial infarctions, strokes, and heart failure events in HealthLNK and compared them with adjudicated events in MESA. Of the 1164 MESA participants enrolled at the Chicago Field Center, 802 (68.9%) participants had data in HealthLNK. The correlation was low for systolic blood pressure (0.39; P<0.0001). In comparison with MESA, HealthLNK overestimated systolic blood pressure by 6.5 mm Hg (95% confidence interval, 4.2-7.8). There was a high correlation between body mass index in MESA and HealthLNK (0.94; P<0.0001). HealthLNK underestimated body mass index by 0.3 kg/m2 (95% confidence interval, -0.4 to -0.1). With the use of International Classification of Diseases, Ninth Revision codes and clinical data, the sensitivity and specificity of HealthLNK queries for hypertension were 82.4% and 59.4%, for obesity were 73.0% and 89.8%, and for diabetes mellitus were 79.8% and 93.3%. In comparison with adjudicated cardiovascular events in MESA, the concordance rates for myocardial infarction, stroke, and heart failure were, respectively, 41.7% (5/12), 61.5% (8/13), and 62.5% (10/16). These findings illustrate the limitations and strengths of electronic data repositories in comparison with information collected by traditional standardized epidemiological approaches for the ascertainment of cardiovascular risk factors and events.


Granuloma inguinale of cervical lymph nodes simulating tuberculous lymphadenitis: two case reports and review of published reports.
Granuloma inguinale (donovanosis) is commonly thought to be a superficial disease, which spreads by continuity and does not affect the regional lymph nodes. Two patients with the disease affecting lymph nodes in the neck are reported from a series of 108 seen in a continuing study of granuloma inguinale. An immunofluorescent antibody test is described that showed antigenic relatedness between the intracellular organisms in these patients and in patients with typical genital granuloma inguinale. Lymphadenitis associated with granuloma inguinale appears to be a stage in the pathogenesis of the pseudobubo, an uncommon feature of this disease.


Nontherapeutic opiate addiction in health professionals: a new form of impairment.
Case studies describe a new type of addicted health professional whose opiate abuse originated recreationally . Historically, health professionals have had high rates of opiate addiction, usually viewed as an occupational hazard stemming from access and from self-treatment for pain or stresses of the medical profession. Partly because addiction in health professionals was almost always therapeutic (iatrogenic) or quasi-therapeutic (stress-related), it affected them less severely than it affected heroin addicts, whose drug abuse usually began recreationally . Now, however, because recreational drug abuse has become commonplace at American colleges since the mid-1960s, a majority of young health professionals have histories of abusing drugs and some are becoming non-therapeutically addicted. Six case studies describe this new addict type, showing how the subjects went from heavy soft drug use to opiate addiction, experienced severe longterm effects, were treated by society, and responded to treatment.


Biomechanical in vitro evaluation of the kangaroo spine in comparison with human spinal data.
On the basis of the kangaroo's pseudo-biped locomotion and its upright position, it could be assumed that the kangaroo might be an interesting model for spine research and that it may serve as a reasonable surrogate model for biomechanical in vitro tests. The purpose of this in vitro study was to provide biomechanical properties of the kangaroo spine and compare them with human spinal data from the literature. In addition, references to already published kangaroo anatomical spinal parameters will be discussed. Thirteen kangaroo spines from C4 to S4 were sectioned into single-motion segments. The specimens were tested by a spine tester under pure moments. The range of motion and neutral zone of each segment were determined in flexion and extension, right and left lateral bending and left and right axial rotation. Overall, we found greater flexibility in the kangaroo spine compared to the human spine. Similarities were only found in the cervical, lower thoracic and lumbar spinal regions. The range of motion of the kangaroo and human spines displayed comparable trends in the cervical (C4-C7), lower thoracic and lumbar regions independent of the motion plane. In the upper and middle thoracic regions, the flexibility of the kangaroo spine was considerably larger. These results suggested that the kangaroo specimens could be considered to be a surrogate, but only in particular cases, for biomechanical in vitro tests.


[Monocytic differentiation of bone marrow-derived hematopoietic precursors controlled by mesenchymal stem cell in absence of exogenous hematopoitic growth factors].
To study the hematopoiesis controlled by mesenchymal stem cell (MSC) in the absence of exogenous hematopoietic growth factors in vitro. MSCs were isolated and cultured in vitro, and the hematopoietic growth factors secreted by MSCs were detected with RT-PCR. Mononuclear cells from bone marrow were seeded in 6-well plates in which MSCs had been seeded as feeder cells. After culture for 3 weeks, cells in coculture were observed with wright's staining, immunocytochemisty and flow cytometry analysis to identify the lineage of hematopoietic cells. The results showed that SCF, Flt3 Ligand and M-CSF were detected in MSCs, but G-CSF and GM-CSF were not detected. In the coculture system, a number of round shape cells grew adherently to the spindle shape MSCs after coculture for 2 weeks. Wright's staining displayed that the round shape cells had abundant plasma and kidney-shaped or oval nucleus, some cells had typical monocytic morphology, and Flow cytometry analysis displayed that the CD45+ round shape cells were positive for CD14 and were negative for CD15, CD7, CD19, CD41 and glycoporin A. Our data suggested that hematopoietic precursors from bone marrow were able to differentiate into monocyte controlled by mesenchymal stem cells in vitro in absence of exogenous hematopoitic growth factors, the committed differentiation might be regulated by the hematopoietic growth factors secreted by MSCs, and the cell-cell contact might also contribute to the differentiation.


Effect of growth temperature on the cryopreservation of prototheca.
The temperature at which Prototheca spp. were grown determined their response to freezing to -196 degrees C and subsequent thawing. Cells cultured at 35 degrees C were the most sensitive to freezing injury; at lower growth temperatures, resistance to freezing damage was seen. At all culture temperatures examined, the freezing tolerance varied with the age of the culture.


Gene expression profiling in live attenuated Edwardsiella tarda vaccine immunized and challenged zebrafish: insights into the basic mechanisms of protection seen in immunized fish.
Despite the importance and success of vaccine immunization against bacterial diseases in fish, little is known about the molecular mechanisms of vaccine-induced immune protection in teleost fish. In this study, the live attenuated Edwardsiella tarda vaccine strain WED, which has been shown to evoke efficacious protection against edwardsiellosis and ascites diseases in fish, was extensively evaluated for multiple parameters in a 5-week immunization and challenge experiment in zebrafish. The parameters evaluated included the immunologic potency (relative percent survival, RPS), the specific IgM antibody titers and the expression profiles of multiple immune-related gene markers at multiple time points following immunization and challenge. During the 4-week immunization phase, the toll-like receptor (TLR) 5 signaling pathway, the MHC-I antigen processing pathway and cytotoxic T lymphocyte (CTL) responses were activated in succession. In contrast, the MHC-II antigen processing pathway and the markers of CD4(+) T lymphocyte activation were down-regulated, and IgM transcription and specific IgM antibody titers were not significantly induced following immunization. During the 1-week challenge phase, the induction of MHC-I and CTL responses and the inhibition of MHC-II and CD4(+) T cell responses were similarly observed in immunized zebrafish following challenge with wild E. tarda. With the 5-week immunization and challenge model, our data suggest the basic mechanism that underlying the long-lasting protective immunity elicited by WED in zebrafish. This mechanism involved the induction of the TLR-5 signaling pathway, the MHC-I antigen processing pathway and CTL effector function, and CTL function seems play a major role in the protection against E. tarda infection in zebrafish.


An Arabidopsis Callose Synthase, GSL5, Is Required for Wound and Papillary Callose Formation.
Arabidopsis was transformed with double-stranded RNA interference (dsRNAi) constructs designed to silence three putative callose synthase genes: GLUCAN SYNTHASE-LIKE5 (GSL5), GSL6, and GSL11. Both wound callose and papillary callose were absent in lines transformed with GSL5 dsRNAi and in a corresponding sequence-indexed GSL5 T-DNA insertion line but were unaffected in GSL6 and GSL11 dsRNAi lines. These data provide strong genetic evidence that the GSL genes of higher plants encode proteins that are essential for callose formation. Deposition of callosic plugs, or papillae, at sites of fungal penetration is a widely recognized early response of host plants to microbial attack and has been implicated in impeding entry of the fungus. Depletion of callose from papillae in gsl5 plants marginally enhanced the penetration of the grass powdery mildew fungus Blumeria graminis on the nonhost Arabidopsis. Paradoxically, the absence of callose in papillae or haustorial complexes correlated with the effective growth cessation of several normally virulent powdery mildew species and of Peronospora parasitica.


Brisk walking offsets the increase in postprandial TAG concentrations found when changing to a diet with increased carbohydrate.
We tested the hypothesis that 30 min of brisk walking daily would offset the increase in plasma TAG concentrations associated with substituting dietary fat for carbohydrate. Fourteen subjects (six males) aged 57 (sd 5) years underwent three 4 d trials in a counterbalanced order: (i) 4 d on a typical UK diet (40 % energy from fat, 45 % carbohydrate and 15 % protein); (ii) 4 d on an isoenergetic diet but substituting fat for carbohydrate in line with the present recommendations (30 % fat, 55 % carbohydrate and 15 % protein); (iii) 4 d on the same recommended diet with 30 min of brisk walking each day. The food provided for the first 3 d of each trial was isoenergetic with each volunteer's previously determined daily energy intake. On day 4, the subjects consumed breakfast, lunch and an early evening meal, equivalent in total to 90 % of their daily energy intake. Blood samples were collected and substrate utilisation and energy expenditure were determined in the fasted state and for 9 h postprandially. Substrate utilisation differed significantly among trials (P = 0.003); RER was higher on the recommended diet trial than during either of the other two trials (P = 0.012 and 0.021 for the UK diet and recommended diet with walking, respectively). The rise in plasma TAG concentrations over the day was steeper on the recommended diet trial than on the other two trials (trial x time interaction, P = 0.040). The increase in postprandial TAG concentrations associated with substituting dietary fat for carbohydrate was offset by 30 min of brisk walking daily.


A ready-to-use antifungal starter culture improves the shelf life of packaged bread.
Fungal spoilage is the main cause of economic loss in the baking industry. In this study, we developed a ready-to-use biopreserver (slurry [SL]) for nonsliced packed bread by using selected antifungal lactic acid bacteria (LAB) and low-cost ingredients that are compatible with the food matrix. Four LAB strains (Lactobacillus brevis CRL 772, L. brevis CRL 796, L. plantarum CRL 778, and L. reuteri CRL 1100) tested in bread preservation were able to inhibit Penicillium sp. growth and lengthen shelf life twofold with respect to breads prepared using only Saccharomyces cerevisiae (2 days shelf life). The best biopreservation effect (5 days shelf life) was obtained with 40% antifungal slurry SL778 containing L. plantarum CRL 778; this was as effective as 0.2% calcium propionate (PCa). The antifungal effect of SL778 was related to the synthesis of acetic and phenyllactic acid as well as lactic acid, which was produced at a high concentration (31.2 mmol/kg) and lowered the pH of the dough, favoring the undissociated fraction of the organic acids. The combination of the starter SL778 with 0.4% PCa extended the shelf life of packaged bread to 24 days, 2.6-fold longer than breads prepared with only 0.4% PCa.


In vitro evaluation of ethanolic extracts of Ageratum conyzoides and Artemisia absinthium against cattle tick, Rhipicephalus microplus.
In vitro efficacy of ethanolic extracts obtained from the aerial parts of Ageratum conyzoides and Artemisia absinthium was assessed on Rhipicephalus microplus using adult immersion test (AIT). Five concentrations of the extract (1.25%, 2.5%, 5%, 10%, and 20%) with three replications for each concentration were used in the bioassay. In AIT, the maximum mortality was recorded as 40% and 66.7% at 20% concentration for A. conyzoides and A. absinthium, respectively. Acaricidal activity was found to be higher in the extract of A. absinthium with LC50 and LC95 values of 11.2% and 61.7%, respectively. Egg mass weight of the live ticks treated with different concentrations of the extracts was significantly (P<0.05) lower than that of control ticks; consequently, the reproductive index and oviposition values of the treated ticks were reduced significantly (P<0.05). The A. conyzoides inhibited 90% hatching of eggs at the 20% concentration, whereas A. absinthium showed 100% inhibition at 5%, 10%, and 20% concentrations. The results show that A. absinthium has better acaricidal properties than A. conyzoides and could be useful in controlling R. microplus.


Imaging of aortic atherosclerotic lesions by (125)I-LDL, (125)I-oxidized-LDL, (125)I-HDL and (125)I-BSA.
The aim of the present study was to compare the accumulation of (125)I-labeled low-density lipoproteins (LDL), oxidized LDL (oxLDL), HDL and BSA in advanced atherosclerotic lesions of apoE-deficient mice. (125)I-lipoproteins or (125)I-BSA were injected into the tail vein of apoE-deficient mice. Blood clearance of (125)I-lipoproteins and (125)I-BSA and their accumulation in atherosclerotic lesions were assayed. Blood clearance of (125)I-LDL and (125)I-HDL was moderate, and approximately 30% of the injected lipoproteins were present in plasma 24 h following injection. oxLDL was removed much faster from plasma, and less than 10% of (125)I-oxLDL was present in the circulation 30 min after (125)I-oxLDL injection. The clearance of (125)I-BSA from the circulation was slower than the lipoprotein clearance. The highest accumulation of LDL, oxLDL, HDL and BSA was detected in atherosclerotic lesions in the aortic arch and abdominal aorta, while lower accumulation was detected in the less atherosclerotic descending thoracic aorta. Our findings demonstrate that both (125)I-HDL and (125)I-BSA as well as (125)I-LDL are accumulated in atherosclerotic plaques and that they can be used for the detection of atherosclerotic lesions.


Temporomandibular joint damage in juvenile idiopathic arthritis: Diagnostic validity of diagnostic criteria for temporomandibular disorders.
Diagnostic criteria reported in the expanded taxonomy for temporomandibular disorders include a standardised clinical examination and diagnosis (DC/TMD 3.B) of temporomandibular joint (TMJ) damage in patients with juvenile idiopathic arthritis (JIA); however, their validity is unknown. To assess the validity of DC/TMD 3.B for the identification of TMJ damage in JIA-patients, using magnetic resonance imaging (MRI) as gold standard, and to investigate the relation between clinical findings and TMJ damage. Fifty consecutive JIA patients (9-16 years) were recruited. DC/TMD 3.B were compared with TMJs MRI (100 TMJs) performed maximum at 1 month from the visit. The severity of TMJ damage was scored in four grades. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), logistic regression models with odds ratio of DC/TMD 3.B and clinical findings respect to MRI were calculated. The DC/TMD 3.B were inadequate in the identification of TMJ damage (sensitivity = 0.15, specificity = 0.92, PPV = 0.85, NPV = 0.28, P = 0.350). Chin deviation and TMJ crepitus were associated with worse TMJ damage (P = 0.006; P = 0.034). Reduced mouth opening (OR = 3.91, P = 0.039) and chin deviation (OR = 13.7, P = 0.014) were associated with the presence of TMJ damage. Combining "pain" (history of pain, TMJ pain, pain during movements) and "function" (TMJ crepitus, reduced mouth opening, chin deviation) clinical findings, the sensitivity and the specificity were 0.88 and 0.54. DC/TMD 3.B present a low sensitivity to diagnose TMJ damage. Chin deviation, reduced mouth opening and TMJ crepitus are associated with TMJ damage. We suggest combining "pain" and "function" findings for the evaluation of TMJ damage in JIA patients.


[House dust mite allergy--living with the invisible roommates].
House dust mites are the most common sources of allergic sensitization, primarily responsible for the occurrence of various clinical forms of respiratory and skin allergies, but also of certain forms of food allergy. There are many various mite species, of which only a small number are constantly or occasionally found in house dust samples. Mites from Pyroglyphidae family, Dermatophagoides pteronyssinus and Dermatophagoides farinae are most frequently responsible for sensitization of susceptible persons. Other less commonly found species may represent individual primary sources of sensitization, or may cause disease symptoms due to cross-reactivity. The exposure to various mite species within different geographical regions accounts for the generation of various sensitization profiles. Knowing these profiles is important for planning rational specific immunotherapy, which greatly determines its efficacy. The aims of this paper are to review the environment conditions that influence mite incidence and the ways their changes can control allergen amounts in patient homes, to review the allergenic content and the significance of cross-reactivity among mite allergens, and finally, to explain the factors that enable the generation of various sensitization profiles.


The histogenetic origin of cervical mesonephric hyperplasia and mesonephric adenocarcinoma of the uterine cervix studied with immunohistochemical methods.
Forty-four cases of mesonephric hyperplasia (MH) and two adenocarcinomas arising from mesonephric remnants (MA) in the cervix were compared immunohistochemically with 10 embryonic and fetal mesonephric tissues. The mesonephric cells retained their pattern for intermediate filaments during ontogenesis, as well as in the mature, hyperplastic, and neoplastic states: they expressed cytokeratin 8, cytokeratin 13, and vimentin, the two latter in variable amounts. In embryonic mesonephric tissues, cytokeratin was absent, whereas the staining for vimentin was intense. Fetal mesonephric cells stained for cytokeratin 13 and vimentin, but that staining diminished as maturation progressed. All MH and MA expressed cytokeratin 8, whereas only 20-30% of the cells in MH and 10-20% of carcinomatous mesonephric cells showed positive reactions with anti-cytokeratin 13 and anti-vimentin. CEA was always negative in cells of mesonephric origin. We regard these results to be important, since the reactions with anti-CEA and anti-vimentin enable one to distinguish cervical adenocarcinomas of mesonephric origin from those of endocervical origin, the latter being CEA-positive and vimentin-negative. Clinical studies revealed that approximately 75% of the patients with MH had used oral contraceptives for several years, 46% had precancerous lesions of the cervix, and in 62% the cervical mucosa showed adenomatous microglandular hyperplasia. We believe that hyperplasia of mesonephric remnants in the cervix may occur more often in patients with disturbed hormonal balance. However, the lack of a control population does not enable us to advance this hypothesis with assurance.


The complexities of postcolonial international health: Karl Evang in India 1953.
In February and March 1953, a WHO Visiting Team of Medical Scientists worked in India, collaborating with local medical students and professionals. This article studies the complexities of early postcolonial international health work and the relations between the young WHO and the newly independent countries, from the position of the team's vice chairman, Norwegian doctor Karl Evang. While the WHO aimed to create dialogue and interaction, also learning from the host country, the article finds that an equal exchange of views between visitors and hosts was not achieved. The topic pertains to discussions on power and influence in international organisations and governance, development and health work, within a South Asian setting. Studying intellectual exchanges between Evang and his Indian interlocutors sheds light on India's role as both receptive and generative site of ideas and political practice, contributing to broader debates on the appropriation, refashioning and application of political ideas in independent India. Also, at a time of new directions in international health, and considering Evang's social medicine conviction, an additional question concerns the role of social medicine. The article underlines the existence of multiple, parallel tracks in international health work, and argues the need to portray international health as a complex mosaic, rather than a step-by-step development. The case has relevance as historians endeavour to make international and global history more diverse, as through Evang we capture parts of a broader international involvement of people and nation states in the WHO and its work in the early post-war period.


A computer-assisted device for the intraoperative CT-correlated localization of brain tumors.
In a series of 72 open brain tumor operations the 32P (radiophosphorus) test proved to be valuable for the removal of visually not detectable tumor residues. As during resection a topographical orientation in the depth of tumor cavities was nearly impossible, a computerized measuring device was developed which enables the surgeon to locate the tumor boundaries by simultaneous comparison with preoperative CT scans. For 32P-beta emission measurements a miniature semiconductor probe can be attached to the tip of the four-axis digitizing arm allowing the evaluation of radicality by topographic distinction between tumor ramifications and normal brain tissue. The device was tested during 3 craniotomies and the perspectives of computerized stereotaxy are discussed.


The revised brain symmetry index.
Recently, the extended brain symmetry index (BSI) was introduced to assist the visual interpretation of the EEG, in particular to quantify both the spatial (left-right) and the temporal spectral characteristics. The BSI has found application in monitoring during carotid endarterectomy, acute stroke and focal seizure detection. Here, we present additional relevant characteristics and a slightly modified version of this index, simulating its behavior as may occur in various clinical conditions, with an emphasis on the detection of cerebral ischaemia. The behavior of the revised and standard sBSI and tBSI is illustrated using random noise signals to simulate various changes in the EEG. The indices are evaluated as a function of spatial and temporal changes, and as a function of the number of channels. The r-sBSI and the r-tBSI are normalized in the range [0-1] with sensitivities of about 0.05 for a 10% difference in signal amplitude, either spatial or temporal. The baseline value of the sBSI shows a modest dependence on the number of channels used. The revised BSI has an improved sensitivity (about two times) to detect interhemispheric asymmetry and diffuse changes. The modified expression of the tBSI is more compact and allows a more intuitive understanding than previously proposed. qEEG assists in a more objective interpretation of the EEG, and is relevant in neuromonitoring.


Rare occurrence of intracranial epidermoid tumor in an unusual location with atypical radiological features.
Intracranial epidermoid tumors are benign rare tumors that arise due to dysembryogenesis. Thought rare, they have characteristic radiological features such as their magnetic resonance imaging signal intensities and a typical location. We present a rare case of intracranial epidermoid tumor in a young female patient that was unusually located within the left frontal lobe and had certain atypical radiological findings. Preoperatively, this lesion was erroneously presumed to be a low grade glioma or a dermoid. Therefore, this case report prompts us to include atypical epidermoid cyst in the list of differential diagnosis for nonenhancing lobar tumors.


KLF2 suppresses TGF-beta signaling in endothelium through induction of Smad7 and inhibition of AP-1.
The flow-responsive Kruppel-like factor 2 (KLF2) is crucial for maintaining endothelial cell quiescence. Here, we describe its detailed effects on transforming growth factor-beta (TGF-beta) signaling, which normally has proatherogenic effects on endothelium. In-depth analysis of genome-wide expression data shows that prolonged lentiviral-mediated overexpression of KLF2 in human umbilical vein endothelial cells (HUVECs) diminishes the expression of a large panel of established TGF-beta-inducible genes. Both baseline and TGF-beta-induced expression levels of plasminogen activator inhibitor 1 (PAI-1) and thrombospondin-1 are greatly diminished by KLF2. Using a combination of ectopic expression, small interfering RNA-mediated knockdown, and promoter activity assays, we show that KLF2 partly inhibits the phosphorylation and subsequent nuclear accumulation of Smad2, thereby suppressing the TGF-beta-induced Smad4-mediated transcriptional activity. This is achieved through TGF-beta-independent induction of inhibitory Smad7. Additionally, a full inhibition of TGF-beta signaling is functionally achieved through a simultaneous suppression of activator protein 1 (AP-1), which is an essential cofactor for TGF-beta-dependent transcription of many genes. The concerted mechanism by which KLF2 inhibits TGF-beta signaling through induction of inhibitory Smad7 and attenuation of AP-1 activity provides a novel mechanism by which KLF2 contributes to sustaining a quiescent, atheroprotective status of vascular endothelium.


Ab initio centroid path integral molecular dynamics: application to vibrational dynamics of diatomic molecular systems.
An ab initio centroid molecular dynamics (CMD) method is developed by combining the CMD method with the ab initio molecular orbital method. The ab initio CMD method is applied to vibrational dynamics of diatomic molecules, H2 and HF. For the H2 molecule, the temperature dependence of the peak frequency of the vibrational spectral density is investigated. The results are compared with those obtained by the ab initio classical molecular dynamics method and exact quantum mechanical treatment. It is shown that the vibrational frequency obtained from the ab initio CMD approaches the exact first excitation frequency as the temperature lowers. For the HF molecule, the position autocorrelation function is also analyzed in detail. The present CMD method is shown to well reproduce the exact quantum result for the information on the vibrational properties of the system.


Challenging Opinion 83.
The Judicial Commission has ruled that subgenus names within the genus Moraxella should be considered to have been included on the Approved Lists, together with the corresponding species names within these subgenera. Closer examination of the facts, including the wording of the relevant passages in the Code and the original publication in which these names are included, together with information that has subsequently come to light, indicates that there is good cause to re-examine the facts on which this Opinion is based.


Two discoveries, one principle: Using a two-stage Bayesian model to explain a dissociated working memory distraction effect.
How working memory (WM) resists perceptual distraction with its limited capacity is a fundamental question to understand its mechanism. To address this question, we used a continuous recall paradigm to directly compare the distraction effect during encoding and the delay periods. Across Experiments 1-3, we observed a substantial distraction-related cost on mnemonic fidelity when distractors presented during the delay (delay-distraction condition), but not if they were introduced at encoding (encoding-distraction condition) or across both periods (full-distraction condition). However, the distraction cost revived when we increased the difficulty to distinguish distractors from targets (Experiments 4 and 4S) and when we changed distractors' relevant features during the delay (Experiment 5). We also found that the robust distraction cost in the delay-distraction condition did not occupy extra spatial resources (Experiments 6a and 6b). These results suggested a dissociated distraction effect, which could be related to the dynamic resource allocation across two WM periods. Here, we proposed a Bayesian model and considered the task relevance and visual uncertainty as two main factors that determine the resource allocation principle at two different stages. This model successfully captured the main findings across all behavioral experiments and performed better than other alternative models. Taken together, the current work advanced our understanding of the distraction resistance of WM under the framework of limited resource allocation. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Stereospecific synthesis of cryptophycin 1.
[reaction: see text] A brief stereospecific synthesis of cryptophycin 1 is described in which (R)-mandelic acid serves as the sole source of asymmetry for unit A. The key step is a hetero-Diels-Alder cycloaddition.


Advances and challenges in uncovering cold tolerance regulatory mechanisms in plants.
Contents Summary I. Introduction II. Cold stress and physiological responses in plants III. Sensing of cold signals in plants IV. Messenger molecules involved in cold signal transduction V. Cold signal transduction in plants VI. Conclusions and perspectives Acknowledgements References SUMMARY: Cold stress is a major environmental factor that seriously affects plant growth and development, and influences crop productivity. Plants have evolved a series of mechanisms that allow them to adapt to cold stress at both the physiological and molecular levels. Over the past two decades, much progress has been made in identifying crucial components involved in cold-stress tolerance and dissecting their regulatory mechanisms. In this review, we summarize recent major advances in our understanding of cold signalling and put forward open questions in the field of plant cold-stress responses. Answering these questions should help elucidate the molecular mechanisms underlying plant tolerance to cold stress.


The regulation of the biosynthesis of ubiquinone in the rat.
The urinary excretion of p-hydroxybenzoate was not altered by ubiquinone feeding, but, although decreased considerably, was not eliminated in protein deficiency. The incorporation of p-hydroxy[U-14C]benzaldehyde into ubiquinone in vivo increased in cold-exposed and p-chlorophenoxyisobutyrate (clofibrate)-fed rats, and these changes were parallel with the changes in the incorporation of [2-14C]mevalonate under these conditions. Starvation, cholesterol feeding and cholic acid feeding resulted in the decreased incorporation of p-hydroxy[U-14C]benzaldehyde into ubiquinone, confirming the decreased ubiquinone synthesis. Feeding exogenous ubiquinone increased the hepatic ubiquinone concentration, but did not cause any decrease in the incorporation of p-hydroxy[U-14C]benzaldehyde into ubiquinone, indicating the absence of a feedback control.


Penetrating neck injury by a sickle.
CT scan is the most important investigation in patients with penetrating neck injury in which it can show the extent of internal injury which may be overlooked. Without CT scan being performed, one should not try to remove foreign body by just pulling blindly, as it can injure vital structures.


Diagnostic performance of an Aspergillus-specific nested PCR assay in cerebrospinal fluid samples of immunocompromised patients for detection of central nervous system aspergillosis.
Central nervous system (CNS) invasive aspergillosis (IA) is a fatal complication in immunocompromised patients. Confirming the diagnosis is rarely accomplished as invasive procedures are impaired by neutropenia and low platelet count. Cerebrospinal fluid (CSF) cultures or galactomannan (GM) regularly yield negative results thus suggesting the need for improving diagnostic procedures. Therefore the performance of an established Aspergillus-specific nested polymerase chain reaction assay (PCR) in CSF samples of immunocompromised patients with suspicion of CNS IA was evaluated. We identified 113 CSF samples from 55 immunocompromised patients for whom CNS aspergillosis was suspected. Of these patients 8/55 were identified as having proven/probable CNS IA while the remaining 47 patients were classified as having either possible (n = 22) or no CNS IA (n = 25). PCR positivity in CSF was observed for 8/8 proven/probable, in 4/22 possible CNS IA patients and in 2/25 NoIA patients yielding sensitivity and specificity values of 1.0 (95% CI 0.68-1) and 0.93 (95% CI 0.77-0.98) and a positive likelihood ratio of 14 and negative likelihood ratio of 0.0, respectively, thus resulting in a diagnostic odds ratio of ∞. The retrospective analysis of CSF samples from patients with suspected CNS IA yielded a high sensitivity of the nested PCR assay. PCR testing of CSF samples is recommended for patients for whom CNS IA is suspected, especially for those whose clinical condition does not allow invasive procedures as a positive PCR result makes the presence of CNS IA in that patient population highly likely.


Cellulolytic activities of fungi destroying ancient books.
Fungi isolated from destroyed ancient books were found to produce active cellulolytic enzymes on various cellulosic substrates. The activity of enzymes from different fungi depended on time of growth and temperature and was independent of growth rate. The isolated fungi degraded cellulose faster at 15 degrees C than at 28 degrees C. The different cellulolytic activities of the fungi may reflect their varied roles in the decomposition of ancient paper.


Triiodothyronine (T3) toxicosis with hypokalemic periodic paralysis.
A case of triiodothyronine (T3) toxicosis associated with hypokalemic periodic paralysis is reported. Thyrotoxic manifestation was minimal except for mild struma. Serum T3 levels were moderately elevated, though other thyroid function tests were within the normal range. The patient was treated with methimazole, and paralytic attacks ceased. This is the first report of this combination and the necessity of careful thyroid function tests in sporadic periodic paralysis is emphasized.


Transcriptional profiles for distinct aggregation states of mutant Huntingtin exon 1 protein unmask new Huntington's disease pathways.
Huntington's disease is caused by polyglutamine (polyQ)-expansion mutations in the CAG tandem repeat of the Huntingtin gene. The central feature of Huntington's disease pathology is the aggregation of mutant Huntingtin (Htt) protein into micrometer-sized inclusion bodies. Soluble mutant Htt states are most proteotoxic and trigger an enhanced risk of death whereas inclusions confer different changes to cellular health, and may even provide adaptive responses to stress. Yet the molecular mechanisms underpinning these changes remain unclear. Using the flow cytometry method of pulse-shape analysis (PulSA) to sort neuroblastoma (Neuro2a) cells enriched with mutant or wild-type Htt into different aggregation states, we clarified which transcriptional signatures were specifically attributable to cells before versus after inclusion assembly. Dampened CREB signalling was the most striking change overall and invoked specifically by soluble mutant Httex1 states. Toxicity could be rescued by stimulation of CREB signalling. Other biological processes mapped to different changes before and after aggregation included NF-kB signalling, autophagy, SUMOylation, transcription regulation by histone deacetylases and BRD4, NAD+ biosynthesis, ribosome biogenesis and altered HIF-1 signalling. These findings open the path for therapeutic strategies targeting key molecular changes invoked prior to, and subsequently to, Httex1 aggregation.


Dissolution of steel slags in aqueous media.
Steel slag is a major industrial waste in steel industries, and its dissolution behavior in water needs to be characterized in the larger context of its potential use as an agent for sequestering CO2. For this purpose, a small closed system batch reactor was used to conduct the dissolution of steel slags in an aqueous medium under various dissolution conditions. In this study, two different types of steel slags were procured from steel plants in India, having diverse structural features, mineralogical compositions, and particle sizes. The experiment was performed at different temperatures for 240 h of dissolution at atmospheric pressure. The dissolution rates of major and minor slag elements were quantified through liquid-phase elemental analysis using an inductively coupled plasma atomic emission spectroscopy at different time intervals. Advanced analytical techniques such as field emission gun-scanning electron microscope, energy-dispersive X-ray, BET, and XRD were also used to analyze mineralogical and structural changes in the slag particles. High dissolution of slags was observed irrespective of the particle size distribution, which suggests high carbonation potential. Concentrations of toxic heavy metals in the leachate were far below maximum acceptable limits. Thus, the present study investigates the dissolution behavior of different mineral ions of steel slag in aqueous media in light of its potential application in CO2 sequestration.


Chemically modified superhydrophobic WO(x) nanowire arrays and UV photopatterning.
A facile route is reported for the fabrication of superhydrophobic tungsten oxide (WO(x)) nanowire surfaces through the chemical adsorption of alkyltrichlorosilane with a static water contact angle (CA) of 163.5 degrees. It is confirmed that CAs on the superhydrophobic surface decreased gradually under UV illumination because of the UV-assisted decomposition of alkyltrichlorosilane chemically adsorbed onto the surface. Superhydrophobic-superhydrophilic switching is also demonstrated by alternating self-assembled monolayer deposition and UV irradiation on the photopatterned nanowire surfaces. Furthermore, the superhydrophobic surface could be transformed selectively into a hydrophilic state by simply exposing the surface to UV through a shadow mask. These studies provide a relatively simple strategy for the design of superhydrophobic surfaces.


Characterization of class 1 integron gene cassettes among clinical bacteria isolated from one large hospital in northern China.
The class 1 integron and complex gene cassettes among different species of clinical isolates in northern China were characterized in this study. 383 clinical isolates were obtained from northern China, and class 1 integrons containing gene cassettes widely distributed among gram negative clinical isolates was observed. We find that the class 1 integron showed positive correlation with multidrug resistance phenotype of gram negative bacteria. In addition, we find that isolates belonged to one species harbored different types of gene cassette arrays, while same types of gene cassette arrays were observed in different species of isolates. The diversity of gene cassette arrays among the isolates indicated the complexity of multidrug resistance in clinical isolates in northern China.


Nontarget Screening Reveals Time Trends of Polar Micropollutants in a Riverbank Filtration System.
The historic emissions of polar micropollutants in a natural drinking water source were investigated by nontarget screening with high-resolution mass spectrometry and open cheminformatics tools. The study area consisted of a riverbank filtration transect fed by the river Lek, a branch of the lower Rhine, and exhibiting up to 60-year travel time. More than 18,000 profiles were detected. Hierarchical clustering revealed that 43% of the 15 most populated clusters were characterized by intensity trends with maxima in the 1990s, reflecting intensified human activities, wastewater treatment plant upgrades and regulation in the Rhine riparian countries. Tentative structure annotation was performed using automated in silico fragmentation. Candidate structures retrieved from ChemSpider were scored based on the fit of the in silico fragments to the experimental tandem mass spectra, similarity to openly accessible accurate mass spectra, associated metadata, and presence in a suspect list. Sixty-seven unique structures (72 over both ionization modes) were tentatively identified, 25 of which were confirmed and included contaminants so far unknown to occur in bank filtrate or in natural waters at all, such as tetramethylsulfamide. This study demonstrates that many classes of hydrophilic organics enter riverbank filtration systems, persisting and migrating for decades if biogeochemical conditions are stable.


Surgical patients with pseudomembranous colitis: factors affecting prognosis.
Although several studies have identified the factors that contribute to the development of antibiotic-associated colitis (AAC), little data are available in regard to those factors that may affect the prognosis of patients with the disease. Therefore we conducted a retrospective analysis of 201 surgical patients with AAC to identify risk factors predictive of increased morbidity or mortality. We conducted a review of the charts of 201 surgical patients hospitalized between Jan. 1, 1991, and June 30, 1993, in whom AAC developed. AAC was defined as the presence of diarrhea associated with a positive latex agglutination or toxin assay for Clostridium difficile. An additional 52 procedure-matched charts of patients admitted to a surgical service during the same period were also reviewed and constituted the control group. We analyzed the contribution of 21 variables to prognosis in both groups. There was no difference between the two groups in the preoperative length of stay, the number of antibiotics per patient and the number of antibiotic-days, number of patients receiving preoperative bowel preparation, total parenteral nutrition, and overall mortality rate. Patients in the control group were at increased risk of death if they had a history of preexisting renal dysfunction, prolonged preoperative hospital stay, and a poor nutritional status. AAC developed 10.0 +/- 13.8 days after operation in the study group. All patients were receiving multiple antibiotics at the time of diagnosis (3.6 +/- 7.5 antibiotic), with a mean of 14.3 +/- 20.7 antibiotic-days. The overall mortality rate in the study group was 8%. In five patients (2%) toxic megacolon developed; four deaths occurred among these patients (80% mortality rate). A 25% mortality rate was directly attributable to complications of AAC. Six variables were identified as predictive of increased mortality rate: steroids, laxatives, length of preoperative stay, postoperative interval before the onset of symptoms, use of total parenteral nutrition, and abdominal distention. AAC carries a significant mortality rate in surgical patients; therefore the diagnosis of AAC should be aggressively pursued and patients with the disease should be promptly treated. Patients receiving steroids, total parenteral nutrition, and multiple antibiotics in whom signs and symptoms of AAC develop late in their postoperative course, and patients with abdominal distention and marked leukocytosis, are at increased risk of dying of AAC and should be aggressively treated.


Topical application of imatinib mesylate ameliorated psoriasis-like skin lesions in imiquimod-induced murine model via angiogenesis inhibition.
Psoriasis is a chronic skin disorder characterized by a skin rash with scaly patches. Microvascular abnormalities are a characteristic feature of psoriasis and play a crucial role in the pathogenesis of psoriatic lesions. Angiogenic factors are upregulated in psoriatic skin lesions and are thought to induce angiogenesis. Platelet-derived growth factor (PDGF) induces vascular endothelial growth factor (VEGF), and PDGF is upregulated in keratinocytes in psoriatic skin lesions. The present study aimed to investigate the effect of topical imatinib mesylate (IMT) in inhibiting the activation of PDGF signalling in the pathogenesis of psoriasis. When topically applied to the skin of mice with imiquimod (IMQ)-induced psoriasis, IMT ameliorated skin symptoms similar to those of human psoriasis. Hyperproliferation of keratinocytes, hyperkeratosis, inflammatory cell infiltration and hypervascularity were histologically suppressed by topical IMT. The expression of angiogenic factors including fibroblast growth factor (FGF) and VEGF was decreased. The expression of FGF and VEGF in a PDGF-stimulated fibroblast cell line was inhibited by IMT. PDGF is required for the signalling pathway producing angiogenic factors in fibroblast. Thus, topically applied IMT inhibits PDGFR activation in fibroblast and suppresses the production of angiogenic factors, thereby mitigating the symptoms of psoriasis. The inhibitory effect of IMT on angiogenesis suggests that topical application IMT may be a viable treatment option for psoriasis.


Limb Misidentification: A Clinical-Anatomical Prospective Study.
The misidentification of one's own limb (LM) after right hemisphere stroke is a striking phenomenon that is incompletely understood. The authors prospectively studied the natural history and anatomy of LM in 36 patients with hyperacute right middle cerebral artery infarct. Unlike in previous studies, rapid clinical assessment was prioritized. The authors found LM to be common and transient, involving 61% at onset, evolving to 15% at 1 week. Voxel-based lesion-symptom mapping found supramarginal gyrus (SMG) damage associated with LM. This substantiates the SMG's importance in LM and has broader implications for lesion analysis: timing matters. Rapid assessment of transient disorders minimizes false negatives, which can improve lesion analysis.


Background documentation of evaluation of occupational exposure to airborne asbestos.
This review presents background information and literature documentation to supplement the "Recommended Procedures for Sampling and Counting Asbestos Fibers: Procedures for the Evaluation of Occupational Exposure to Airborne Asbestos" prepared by the joint ACGIH-AIHA Aerosol Hazards Evaluation Committee. It reviews the nature of the inhalation hazard associated with asbesots fibers, the sampling and analytic methods which have been used, and a rationale for the selection of the membrane filter sampling-optical phase microscope identification and assay methodology which is recommended.


One-step formation of TiO2 hollow spheres via a facile microwave-assisted process for photocatalytic activity.
Mesoporous TiO2 hollow spherical nanostructures with high surface areas were successfully prepared using a microwave method. The prepared hollow spheres had a size range between 200 and 500 nm. The spheres consisted of numerous smaller TiO2 nanoparticles with an average diameter of 8 nm. The particles had an essentially mesoporous structure, with a pore size in the range of 2-50 nm. The results confirmed that the synthesised of anatase TiO2 nanoparticles with specific surface area approximately 172.3 m2 g-1. The effect of ultraviolet and visible light irradiation and catalyst dosage on the TiO2 photocatalytic activity was studied by measuring the degradation rate of methylene blue. The maximum dye degradation performances with low catalyst loading (30 mg) were 99% and 63.4% using the same duration of ultraviolet and visible light irradiation, respectively (120 min).


Asymmetric Dimethylarginine Induced Apoptosis and Dysfunction of Endothelial Progenitor Cells: Role of Endoplasmic Reticulum Stress Pathway.
Asymmetric dimethylarginine (ADMA), an inhibitor of nitric oxide synthase, is a novel risk factor of cardiovascular disease. Endothelial progenitor cells (EPCs) bear typical endothelial characteristics and are thought to contribute to neovascularization by providing new endothelial cells (ECs) after arterial injury. Many studies have shown that ADMA can induce EPC apoptosis and dysfunction, but the underlying mechanism is not well understood. EPCs from umbilical cord blood were cultured in EGM-2 medium with particular growth factors and supplemented with 10% fetal bovine serum. The cells were treated with different concentrations of ADMA (5, 10, and 50 μmol/L). Endoplasmic reticulum (ER) stress marker levels were examined by western blot analysis. After 24-hour incubation, ADMA induced apoptosis of EPCs and significantly decreased the proliferation, migration, and vasculogenesis capacity of EPCs. We also found that ADMA treatment activated phosphorylated protein kinase RNA-activated-like ER kinase (PERK), a stress sensor protein in the endoplasmic reticulum (ER). The activated PERK induced 78 kDa glucose-regulated protein (GRP-78) and C/EBP homologous protein (CHOP) expression. Additionally, the inhibition of the ER stress pathway by Salubrinal (a specific ER stress inhibitor) can attenuate ADMA-induced apoptosis of EPCs. Overall, these observations indicate that ADMA may induce the apoptosis and dysfunction of EPCs through the ER stress pathway.


Are Bone Bruise Characteristics and Articular Cartilage Pathology Associated with Inferior Outcomes 2 and 6 Years After Anterior Cruciate Ligament Reconstruction?
Objective To determine (1) if bone bruise characteristics seen on magnetic resonance imaging are associated with patient-reported outcomes prior to and following anterior cruciate ligament reconstruction and (2) if the combined presence of bone bruises with articular cartilage pathology results in inferior 2- or 6-year outcomes. Design Bone bruise volume and severity were measured on 81 patients' preoperative magnetic resonance imaging in the medial and lateral femoral condyle (MFC, LFC) and medial and lateral tibial plateau (MTP, LTP) using the Costa-Paz classification and a modified version of Roemer and Bohndorf's technique. The relationships between bone bruise volume and severity with Knee Injury and Osteoarthritis Outcome Score (KOOS) and International Knee Documentation Committee (IKDC) scores were assessed, and pre- and postoperative KOOS and IKDC scores were compared between those with bone bruises either with or without combined local articular cartilage pathology. Results All 81 patients had a bone bruise in at least 1 region and 70 (86%) had bone bruises in ≥2 regions. LTP bruises were the most common (76/81, 94%), followed by the LFC (66, 81%), MTP (46, 57%), and MFC (20, 25%). Neither bone bruise volume nor severity was associated with inferior postoperative outcomes. The subset of 17 patients with bone bruises and combined articular cartilage pathology were 3.4 times more likely to be symptomatic at 6-year follow-up than those without articular cartilage pathology ( P = 0.04). Conclusions The volume and severity of preoperative bone bruises alone were not associated with 2- or 6-year outcomes; however, bone bruises combined with local articular cartilage pathology appear to be more symptomatic after ACL reconstruction.


Longitudinal study on growth and body mass index before and after diagnosis of childhood craniopharyngioma.
We analyzed whether childhood craniopharyngioma predisposes to obesity and growth impairment. Height/length, body mass index (BMI), and hypothalamic involvement were evaluated in 90 patients at standardized ages and time points before, after, and at the time of diagnosis. Relevant decreases in height sd score (SDS) started at 10-12 months of age and persisted until diagnosis of childhood craniopharyngioma. Relevant increases in BMI SDS were detectable between 4 and 5 yr of age. Postoperative BMI SDS (yr 1-6) had a weak positive correlation with BMI SDS at the time of diagnosis. In linear regression analysis, hypothalamic tumor involvement (P < 0.001), ponderal index at birth (P = 0.014), and BMI SDS at age 6-7 months (P = 0.029) and at age 5 yr (P < 0.001) had relevant and independent impacts on the development of obesity. Patients with hypothalamic involvement (n = 48) presented lower ponderal index and BMI SDS at birth and higher BMI SDS at the time of diagnosis (P < 0.001) as well as during annual follow-up (P < 0.001) compared with patients without hypothalamic involvement (n = 42). From childhood (3.5-4 yr) to the time of diagnosis, growth rates were reduced for patients with hypothalamic tumor involvement. Patients without hypothalamic involvement presented reduced growth rates in early infancy (age 10-12 months) that persisted until diagnosis. We conclude that reduced growth rates occur quite early in history; BMI SDS increases occur later and are predictive of obesity. Hypothalamic involvement is the major risk factor for obesity in patients with childhood craniopharyngioma.


Rapidly-Exploring Adaptive Sampling Tree*: A Sample-Based Path-Planning Algorithm for Unmanned Marine Vehicles Information Gathering in Variable Ocean Environments.
This research presents a novel sample-based path planning algorithm for adaptive sampling. The goal is to find a near-optimal path for unmanned marine vehicles (UMVs) that maximizes information gathering over a scientific interest area, while satisfying constraints on collision avoidance and pre-specified mission time. The proposed rapidly-exploring adaptive sampling tree star (RAST*) algorithm combines inspirations from rapidly-exploring random tree star (RRT*) with a tournament selection method and informative heuristics to achieve efficient searching of informative data in continuous space. Results of numerical experiments and proof-of-concept field experiments demonstrate the effectiveness and superiority of the proposed RAST* over rapidly-exploring random sampling tree star (RRST*), rapidly-exploring adaptive sampling tree (RAST), and particle swarm optimization (PSO).


Drugs and sex: 'a survey of college students' beliefs.
71 university students were surveyed regarding the effects of five drugs on human sexuality. Most of the myths examined were believed by a number of the 71 students surveyed. Users of alcohol (n = 62) and cocaine (n = 22) were more accurate in identifying effects than were nonusers.


Simulating Electron Dynamics in Polarizable Environments.
We propose a methodology for simulating attosecond electron dynamics in large molecular systems. Our approach is based on the combination of real time time-dependent-density-functional theory (RT-TDDFT) and polarizable Molecular Mechanics (MMpol) with the point-charge-dipole model of electrostatic induction. We implemented this methodology in the software deMon2k that relies heavily on auxiliary fitted densities. In the context of RT-TDDFT/MMpol simulations, fitted densities allow the cost of the calculations to be reduced drastically on three fronts: (i) the Kohn-Sham potential, (ii) the electric field created by the (fluctuating) electron cloud which is needed in the QM/MM interaction, and (iii) the analysis of the fluctuating electron density on-the-fly. We determine conditions under which fitted densities can be used without jeopardizing the reliability of the simulations. Very encouraging results are found both for stationary and time-dependent calculations. We report absorption spectra of a dye molecule in the gas phase, in nonpolarizable water, and in polarizable water. Finally, we use the method to analyze the distance-dependent response of the environment of a peptide perturbed by an electric field. Different response mechanisms are identified. It is shown that the induction on MM sites allows excess energy to dissipate from the QM region to the environment. In this regard, the first hydration shell plays an essential role in absorbing energy. The methodology presented herein opens the possibility of simulating radiation-induced electronic phenomena in complex and extended molecular systems.


Integration and gene replacement in the Lactococcus lactis lac operon: induction of a cryptic phospho-beta-glucosidase in LacG-deficient strains.
Insertions, replacement mutations, and deletions were introduced via single or double crossover recombination into the lacE (enzyme IIlac) and lacG (phospho-beta-galactosidase) genes of the Lactococcus lactis chromosomal lacABCDFEGX operon. LacG production was abolished in strains missing the lacG gene or carrying multicopy insertions in the lacE gene that affected expression of the lacG gene. However, these LacG-deficient strains could still ferment lactose slowly and were found to contain an enzymatic activity that hydrolyzed the chromogenic substrate o-nitrophenyl-beta-D-galactopyranoside phosphate. Induction of this phospho-beta-glycohydrolase activity coincided with the appearance of a new 55-kDa protein cross-reacting with anti-LacG antibodies that had a size similar to that of LacG but a higher isoelectric point (pI 5.2) and was not found in wild-type cells during growth on lactose. Since the phospho-beta-glycohydrolase activity and this protein with a pI of 5.2 were highly induced in both mutant and wild-type cells during growth on cellobiose that is likely to be transported via a phosphoenolpyruvate-dependent phosphotransferase system, we propose that this induced activity is a phospho-beta-glucosidase that also hydrolyzes lactose-6-phosphate.


Deciphering the Potential Pharmaceutical Mechanism of GUI-ZHI-FU-LING-WAN on Systemic Sclerosis based on Systems Biology Approaches.
Systemic sclerosis (SSc; scleroderma) is a complicated idiopathic connective tissue disease with seldom effective treatment. GUI-ZHI-FU-LING-WAN (GFW) is a classic Traditional Chinese Medicine (TCM) formula widely used for the treatment of SSc. However, the mechanism of how the GFW affects SSc remains unclear. In this study, the system biology approach was utilized to analyze herb compounds and related targets to get the general information of GFW. The KEGG enrichment analysis of 1645 related targets suggested that the formula is involved in the VEGF signaling pathway, the Toll-like receptor signaling pathway, etc. Quantitative and qualitative analysis of the relationship among the 3 subsets (formula targets, drug targets and disease genes) showed that the formula targets overlapped with 38.0% drug targets and 26.0% proteins encoded by disease genes. Through the analysis of SSc related microarray statistics from the GEO database, we also validated the consistent expression behavior among the 3 subsets before and after treatment. To further reveal the mechanism of prescription, we constructed a network among 3 subsets and decomposed it into 24 modules to decipher how GFW interfere in the progress of SSc. The modules indicated that the intervention may come into effect through following pathogenic processes: vasculopathy, immune dysregulation and tissue fibrosis. Vitro experiments confirmed that GFW could suppress the proliferation of fibroblasts and decrease the Th1 cytokine (TNF-α, MIP-2 and IL-6) expression for lipopolysaccharide (LPS) and bleomycin (BLM) stimulation in macrophages, which is consistent with previous conclusion that GFW is able to relieve SSc. The systems biology approach provides a new insight for deepening understanding about TCM.


Biotribology of Synovial Cartilage: A New Method for Visualization of Lubricating Film and Simultaneous Measurement of the Friction Coefficient.
A healthy natural synovial joint is very important for painless active movement of the natural musculoskeletal system. The right functioning of natural synovial joints ensures well lubricated contact surfaces with a very low friction coefficient and wear of cartilage tissue. The present paper deals with a new method for visualization of lubricating film with simultaneous measurements of the friction coefficient. This can contribute to better understanding of lubricating film formation in a natural synovial joint. A newly developed device, a reciprocating tribometer, is used to allow for simultaneous measurement of friction forces with contact visualization by fluorescence microscopy. The software allowing for snaps processing and subsequent evaluation of fluorescence records is developed. The evaluation software and the follow-up evaluation procedure are also described. The experiments with cartilage samples and model synovial fluid are carried out, and the new software is applied to provide their evaluation. The primary results explaining a connection between lubrication and friction are presented. The results show a more significant impact of albumin proteins on the lubrication process, whereas its clusters create a more stable lubrication layer. A decreasing trend of protein cluster count, which corresponds to a decrease in the thickness of the lubrication film, is found in all experiments. The results highlight a deeper connection between the cartilage friction and the lubrication film formation, which allows for better understanding of the cartilage lubrication mechanism.


Magnetic diagnostics for equilibrium reconstruction and realtime plasma control in NSTX-Upgrade.
This paper describes aspects of magnetic diagnostics for realtime control in National Spherical Torus Experiment-Upgrade (NSTX-U). The sensor arrangement on the upgraded center column is described. New analog and digital circuitry for processing the plasma current Rogowski data are presented. An improved algorithm for estimating the plasma vertical velocity for feedback control is presented.


Impaired glymphatic function in idiopathic intracranial hypertension.
Idiopathic intracranial hypertension is a brain disease incorporating cerebrospinal fluid disturbance, increased intracranial pressure and visual failure, but with unknown cause. This study examined a hypothesis that glymphatic function is impaired in idiopathic intracranial hypertension patients. The MRI contrast agent gadobutrol was utilized as a cerebrospinal fluid tracer following intrathecal administration. Consecutive standardized T1 MRI acquisitions over 48 h were done to assess tracer distribution within brain of 15 idiopathic intracranial hypertension patients and 15 reference individuals who were comparable in age and gender distribution. Using FreeSurfer software, we semi-quantified tracer level in multiple brain regions as T1 MRI signal change. The tracer enriched the entire brain of idiopathic intracranial hypertension and reference subjects. In idiopathic intracranial hypertension, tracer enrichment was increased and clearance of tracer delayed from a wide range of brain regions, including both grey and white matter. Differences were most evident in frontal and temporal regions. The pulsatile intracranial pressure was measured overnight and tracer propagation in brain compared between individuals with pathological and normal pulsatile intracranial pressure. In individuals with pathological pulsatile intracranial pressure, tracer enrichment was stronger and clearance from brain delayed, particularly in regions nearby large artery trunks at the brain surface. The present in vivo observations provide evidence for impaired glymphatic function in several brain regions of idiopathic intracranial hypertension patients. Glymphatic failure may imply altered clearance of metabolic byproducts, which may precede neurodegeneration. Further studies are needed to characterize glymphatic failure in idiopathic intracranial hypertension.


On the representational nature of value-driven spatial attentional biases.
Reward learning biases attention toward both reward-associated objects and reward-associated regions of space. The relationship between objects and space in the value-based control of attention, as well as the contextual specificity of space-reward pairings, remains unclear. In the present study, using a free-viewing task, we provide evidence of overt attentional biases toward previously rewarded regions of texture scenes that lack objects. When scrutinizing a texture scene, participants look more frequently toward, and spend a longer amount of time looking at, regions that they have repeatedly oriented to in the past as a result of performance feedback. These biases were scene specific, such that different spatial contexts produced different patterns of habitual spatial orienting. Our findings indicate that reinforcement learning can modify looking behavior via a representation that is purely spatial in nature in a context-specific manner. NEW & NOTEWORTHY The representational nature of space in the value-driven control of attention remains unclear. Here, we provide evidence for scene-specific overt spatial attentional biases following reinforcement learning, even though the scenes contained no objects. Our findings indicate that reinforcement learning can modify looking behavior via a representation that is purely spatial in nature in a context-specific manner.


Abatacept improves both the physical and mental health of patients with rheumatoid arthritis who have inadequate response to methotrexate treatment.
To examine the impact of added abatacept treatment on health related quality of life (HRQoL) in patients with rheumatoid arthritis (RA) who have inadequate response to methotrexate (MTX). The impact of abatacept treatment on HRQoL was examined in a longitudinal, randomised double blind, placebo controlled clinical trial. Effects of treatment on HRQoL were examined using repeated measures analysis of covariance and comparing rates of change in HRQoL across treatment groups. The relationship between American College of Rheumatology (ACR) clinical markers and disease duration with changes in HRQoL indicators was also examined. Finally, a responder analysis was used to examine the percentage of patients who improved by 0.5 SD in 12 months or who reached the normative levels seen in the US general population. Statistically significant improvements in the abatacept group relative to controls were observed across a range of HRQoL measures, including physical function, fatigue, all eight domains of the SF-36, and the physical and mental component summaries (PCS and MCS). Improvements were seen as early as day 29 for fatigue and for five out of eight SF-36 domains. By day 169, all HRQoL measures were significantly better with abatacept than with placebo. HRQoL gains were associated with greater ACR clinical improvement, and the effects were consistent for patients with different disease duration. A significantly greater percentage of patients treated with abatacept reached normative levels of PCS, MCS, physical functioning, and fatigue compared with patients treated with MTX alone. Combined abatacept and MTX treatment produces significant improvements across a wide range of HRQoL domains in patients with RA.


Increase in concanavalin A cap formation on lymphoma cells following interaction with inactive influenza viruses.
Binding of the lectin Con A to its ligand on the cell surface of normal circulating lymphocytes induces capping in 28-32% of these cells. This Con A cap formation is markedly decreased in malignant cells from the human hematopoietic system. Among others, the human lymphoma Daudi cell line exhibit a cap formation with Con A in only 5-10% of the cells. In this study, we found that inactivated influenza viruses induced changes in the cell surface membrane of Daudi cells resulting in an increased percentage of Con A cap forming cells (30-40%). This phenomenon occurred independently of viral replication and was initiated by adsorption of inactivated viral particles or isolated hemagglutinin and neuraminidase viral glycoproteins. This phenomenon may be due to the binding of Con A molecules to viral receptors and to cell receptors leading to crosslinking of Con A receptors that will induce their mobility and the formation of a cap. Alternatively, experiments performed with cytochalasin B and colchicine suggest that the viral interaction with the cell membrane may have induced changes in the cytoskeleton at the level of microtubules. These changes induced increased lateral movement of the Con A receptors resulting into formation of a cap.


Distinction of normal, preneoplastic, and neoplastic mouse mammary primary cell cultures by water nuclear magnetic resonance relaxation times.
Normal, preneoplastic, and neoplastic primary cultures of mouse mammary epithelial cells were distinguishable on the basis of water proton nuclear magnetic resonance (NMR) relaxation times--i.e., spin-lattice relaxation time (T1) and spin-spin relaxation time (T2). T1 values were 916 +/- 24 msec for normal cells, 1,029 +/- 24 msec for preneoplastic cells, and 1,155 +/- 42 msec for neoplastic cells. This method of distinction between normal and neoplastic cells (P less than 0.001) and normal and preneoplastic cells (P less than 0.005) supported previous findings in whole tissues. NMR relaxation times resulted in better distinction between these cell populations than any other technique except direct histology. The T1 and T2 values of water protons in cells grown in primary culture were higher than those of established mouse mammary cancer cell lines. The differences in T1 and T2 did not correlate with cellular hydration. The data suggested a basic difference in water-macromolecular surface interactions among normal, preneoplastic, and neoplastic cells.


[Method of registration of vestibular myogenic evoked potentials in the diagnosis of diseases of the inner ear].
The literature review is devoted to the practical application of the method of recording vestibular evoked myogenic potentials (VEMPs) in the diagnosis of the inner ear diseases: superior semicircular canal dehiscence syndrome, Meniere's disease, benign paroxysmal positional vertigo (BPPV), vestibular neuritis. Registration of VMEP is an electrophysiological research method that allows to assess objectively the functional state of the otolith receptors (sacculus and utriculus) and their pathways, which expands the diagnostic capabilities in diagnosis of the inner ear diseases.


Structural investigations on a peptide regulating hemopoiesis in vitro and in vivo.
Clonal growth in agar of myeloid committed stem cells (CFU-c) is inhibited by a specifically acting "hemoregulatory peptide" which had been isolated from human leukocytes. The inhibitory peptide is composed of aspartic acid, glutamic acid, lysine, cysteine and possibly glycine. It was [3H]carboxymethylated with [3H]iodoacetic acid. From the electrophoretic behaviour of this derivative at pH 1.9 a single positive charge and a molecular mass of about 600-650 Da could be inferred. This positive charge is lost after acetylation and is identified as the epsilon-amino group in the side chain of a lysine residue since the N-terminal group is a pyroglutamic residue. Electrophoresis of the native peptide at pH 6.5 reveals the presence of three carboxyl groups, two of which were localized in the N-terminal part of the molecule, while cysteine and lysine were located in the C-terminal portion. Lysine was identified as the C-terminal residue by a double labeling technique applied to the Cys-[(3H]Cm)-containing fission peptide after partial hydrolysis. Uncertainties in the molecular mass determinations allow for the possible presence of a small residue without reactive side chain (glycine?) in the C-terminal portion of the molecule. The structure of the inhibitory peptide was thus determined as less than Glu-(Asp/Glu)-(Asp/Glu)-Cys-(Gly?)-Lys. This structure is supported by comparison with synthetic peptides. The analogue less than Glu-Glu-Asp-Cys-Lys has properties which are similar to those of the natural inhibitor.


Unraveling the crystallization mechanism of CoAPO-5 molecular sieves under hydrothermal conditions.
The hydrothermal crystallization of CoAPO-5 molecular sieves has been studied using time-resolved in-situ SAXS/WAXS, UV-vis, Raman, and XAS. Data collected during heating to 180 degrees C allowed the observation of different steps occurring during the transformation of the amorphous gel into a crystalline material from a macroscopic and atomic perspective. Raman spectroscopy detected the initial formation of Al-O-P bonds, whereas SAXS showed that these gel particles had a broad size distribution ranging from ca. 7 to 20 nm before crystallization began. WAXS showed that this crystallization was sharp and occurred at around 160 degrees C. Analysis of the crystallization kinetics suggested a one-dimensional growth process. XAS showed that Co(2+) transformed via a two-stage process during heating involving (i) a gradual transformation of octahedral coordination into tetrahedral coordination before the appearance of Bragg peaks corresponding to AFI, suggesting progressive incorporation of Co(2+) into the poorly ordered Al-O-P network up to ca. 150 degrees C, and (ii) a rapid transformation of remaining octahedral Co(2+) at the onset of crystallization. Co(2+) was observed to retard crystallization of AFI but provided valuable information regarding the synthesis process by acting as an internal probe. A three-stage, one-dimensional crystallization mechanism is proposed: (i) an initial reaction between aluminum and phosphate units forming a primary amorphous phase, (ii) progressive condensation of linear Al-O-P chains forming a poorly ordered structure separated by template molecules up to ca. 155 degrees C, and (iii) rapid internal reorganization of the aluminophosphate network leading to crystallization of the AFI crystal structure.


One healthy live birth after preimplantation genetic testing of a cryptic balanced translocation (9;13) in a family with cerebral palsy and glaucoma: a case report.
Cryptic balanced translocations often evade detection by conventional cytogenetics. The preimplantation genetic testing (PGT) technique can be used to help carriers of balanced translocations give birth to healthy offspring; however, for carriers of cryptic balanced translocations, there is only one report about trying assisted reproduction using the PGT technique but with no pregnancy. A couple had 3 births out of 4 pregnancies, and all died very young, with two of them having both cerebral palsy and glaucoma. The husband with oligoasthenospermia was found to be a cryptic balanced translocation carrier for t (9,13) (p24.3, q31.3) with G-banding, FISH (fluorescence in-situ hybridization), and MicroSeq techniques; live birth of a healthy baby girl was achieved with PGT/NGS (next-generation sequencing) for the couple. Here, we report for the first time a successful live birth of a healthy baby through the PGT technique for a family in which the husband is a carrier of the cryptic balanced translocation t (9,13) (p24.3, q31.3), presumably causative for cerebral palsy and glaucoma. Our study showed that the PGT/NGS technique can effectively help families with a cryptic balanced translocation have healthy offspring.


Validation of a commercially available indirect ELISA using a nucleocapside recombinant protein for detection of Schmallenberg virus antibodies.
A newly developed Enzym Like Immuno Sorbant Assay (ELISA) based on the recombinant nucleocapsid protein (N) of Schmallenberg virus (SBV) was evaluated and validated for the detection of SBV-specific IgG antibodies in ruminant sera by three European Reference Laboratories. Validation data sets derived from sheep, goat and bovine sera collected in France and Germany (n = 1515) in 2011 and 2012 were categorized according to the results of a virus neutralization test (VNT) or an indirect immuno-fluorescence assay (IFA). The specificity was evaluated with 1364 sera from sheep, goat and bovine collected in France and Belgium before 2009. Overall agreement between VNT and ELISA was 98.9% and 98.3% between VNT and IFA, indicating a very good concordance between the different techniques. Although cross-reactions with other Orthobunyavirus from the Simbu serogroup viruses might occur, it is a highly sensitive, specific and robust ELISA-test validated to detect anti-SBV antibodies. This test can be applied for SBV sero-diagnostics and disease-surveillance studies in ruminant species in Europe.


Photolytic treatment of atrazine-contaminated water: products, kinetics, and reactor design.
This study investigates the products, kinetics, and reactor design of atrazine photolysis under 254-nm ultraviolet-C (UVC) irradiation. With an initial atrazine concentration of 60 microg/L (60 ppbm), only two products remain in detectable levels. Up to 77% of decomposed atrazine becomes hydroxyatrazine, the major product. Both atrazine and hydroxyatrazine photodecompose following the first-order rate equation, but the hydroxyatrazine photodecomposition rate is significantly slower than that of atrazine. For atrazine photodecomposition, the rate constant is proportional to the square of UVC output, but inversely proportional to the reactor volume. For a photochemical reactor design, a series of equations are proposed to calculate the needed UVC output power, water treatment capacity, and atrazine outlet concentration.


Comparative Analysis of a New Automatic System and Four Existing Techniques for Autologous Fat Grafting.
Autologous fat grafting is increasingly used worldwide and is a very attractive technique in many ways. However, treatment duration and postinjection tissue resorption remain problematic elements, which are largely related to the preparation method used. Moreover, few scientific studies objectively compare different fat preparation methods. This study analyzes the efficiency and quality of lipoaspirates prepared with a new filtration/centrifugation system (Adipure) in comparison with several existing techniques. Patient lipoaspirates were processed by five different techniques: decantation, centrifugation, Macrofill, Puregraft, and Adipure. Adipose tissue was evaluated in vitro for tissue resorption and oil formation, as well as in vivo after subcutaneous injections in immunodeficient mice. Adipose grafts were collected after 1 month, weighed, and analyzed by histology with a detailed scoring method. Decanting gives inferior results to all other techniques, in terms of amount of tissue and oil in vitro, or graft weight and histological analysis in vivo. Methods using classical Coleman centrifugation (1200g), or a modified one (400g) associated with washes (Macrofill) produce very similar results, both in vitro and in vivo. Techniques using filtration systems (Puregraft and Adipure) produce less oil overall and have a higher grafting efficiency. The best results regarding grafting efficiency and oil quantity are found with the Adipure device. A combination of filtration and very low-speed centrifugation potentiates the advantages of these techniques, in terms of graft efficiency. The adipose tissue purification being done in a few minutes, in an automatic way, undoubtedly provides a strong advantage for the use of this new system.


Adenosine receptors and modulation of natural killer cell activity by purine nucleosides.
Natural killer (NK) cell activity is inhibited by the adenosine analogue tubercidin (Tub) and stimulated by the deoxyadenosine analogue 2-fluoro-1-beta-D-arabinofuranosyladenine 5'-monophosphate (F-ara-AMP) in the spleen lymphocytes from mice treated with the drugs in vivo (T. Priebe et al., Cancer Res., 48:4799, 1988). The present report demonstrates that the inhibition by Tub and stimulation by F-ara-AMP of NK cell activity are readily demonstrable in murine and human lymphocytes exposed to the drugs in vitro. In mouse spleen lymphocytes, NK cell activity is also inhibited by adenosine receptor A2 agonists, whereas potent A1 receptor agonists are more effective stimulators. Inhibition produced by adenosine, deoxyadenosine, and adenosine receptor agonists, but not by Tub, is partially prevented by the adenosine receptor antagonist 1,3-dipropyl-8-phenylxanthine amine congener. Agents that stimulate NK cell activity (deoxyadenosine, A1 receptor agonists, F-ara-AMP) do not increase further the 1.5-fold enhancement produced by a 10(-6) M concentration of 1,3-dipropyl-8-phenylxanthine amine congener. The nucleoside transport inhibitor, p-nitrobenzylthioinosine 5'-monophosphate, has no effect on NK cell activity or intracellular ribonucleotide pools; however, it partially prevents Tub 5'-triphosphate formation, ATP depletion, and NK cell inhibition in mouse spleen cells treated with Tub. p-Nitrobenzylthioinosine 5'-monophosphate also partially prevents the F-ara-AMP stimulation of NK cell activity, but it does not influence the effects of adenosine or deoxyadenosine. The results obtained with the adenosine receptor agonists suggest roles for both A1 and A2 receptors in regulating murine NK cell activity. Tub inhibition of NK cell activity does not appear to involve adenosine receptors; however, inhibition by the other agents may be mediated via an A2 receptor (stimulatory for adenylyl cyclase). Since p-nitrobenzylthioinosine 5'-monophosphate inhibited the stimulation of NK cell activity by F-ara-AMP, this stimulation may occur via an intracellular "P" site (inhibitory to adenylyl cyclase).


Strontium isotope analysis of otoliths reveals differences in the habitat salinity among three sympatric stickleback species of the genus Pungitius.
The analysis of otolith Sr isotope ratios (87Sr/86Sr) is a powerful method to study fish migration in freshwater areas. However, few studies have applied this method to study fish movement in brackish-water environments. Furthermore, despite the fact that habitat differentiation has been shown to drive genetic differentiation and reproductive isolation among stickleback fish, no studies have used the otolith 87Sr/86Sr ratios to analyze habitat differentiation between stickleback ecotypes and species. In this study, we analyzed the otolith 87Sr/86Sr ratios of three sympatric stickleback species of the genus Pungitius in the Shiomi River on Hokkaido Island, Japan: P. tymensis, the brackish-water type of the P. pungitius-P. sinensis complex, and the freshwater type of the P. pungitius-P. sinensis complex. First, we created a mixing equation to depict the relationship between habitat salinity and the 87Sr/86Sr ratios of river water. We found that the otolith 87Sr/86Sr ratios differed significantly among the three species, indicating that the three species utilize habitats with different salinities: P. tymensis and the brackish-water type inhabit freshwater and brackish-water environments, respectively, with the freshwater type using intermediate habitats. In addition, we found that some freshwater individuals moved to habitats with higher salinities as they grew. Our study demonstrates that the analysis of otolith 87Sr/86Sr ratios is a useful method for studying the habitat use of fish in brackish-water environments and habitat differentiation among closely related sympatric and parapatric species.


Biomechanical and histologic assessment of a controlled muscle strain injury treated with piroxicam.
This study was designed to observe the effect of the nonsteroidal antiinflammatory piroxicam on a controlled muscle strain injury in the rabbit model. The tibialis anterior tendons of 90 New Zealand White rabbits were detached at their distal insertions, and the right tendon was stretched to the yield point of the deformation curve. One group of 50 rabbits received piroxicam treatment and the others received no treatment. At 1, 2, 4, and 7 days the parameters of muscle function, tensile strength, and histology were examined. Muscle contractile force was significantly greater in the piroxicam-treated group at Day 1, but no difference was noted at any other time period. Tensile strength was not significantly different at any time period in either group. Histology revealed delayed degradation of damaged tissue and slowed regeneration of muscle tissue at the injury site in the piroxicam-treated group. Piroxicam and other anti-inflammatories are frequently given to athletes being treated for muscle strain injuries to control pain through their effect on the inflammatory process. This study demonstrates that piroxicam does not adversely influence the recovery of contractile and tensile strength in a followup period of 1 week. Therefore, antiinflammatory treatment may be beneficial early in the course of muscle injury.


Visor Osteotomy of the Anterior Mandible.
Current techniques for three-dimensional correction of the chin in patients with mandibular retrusion may increase mentolabial fold depth, but have limited effect on the lips. The authors present a single surgical technique to support the mentolabial fold and improve labial competence. The visor osteotomy is performed from canine to canine. The bone fragment pedicled to the lingual periosteum is coronally mobilized and fixed in the new position. Preserved vascularization is supposed to minimize the amount of bone resorbed. Visor osteotomy of the anterior mandible may improve the existing treatments for micrognathia by creating an aesthetic mentolabial fold and a competent lip seal.


Chiral boronate derivatives via catalytic enantioselective conjugate addition of Grignard reagents on 3-boronyl unsaturated esters and thioesters.
There is a growing interest in the development of new methods to prepare chiral organoboronate derivatives in optically pure form. An efficient copper-catalyzed enantioselective conjugate addition methodology using Grignard reagents and 3-boronyl acrylate derivatives was optimized for the preparation of chiral alkylboronate products in high yields and up to 98% ee. The resulting 1,8-diaminonaphthalene adducts can be transformed into the corresponding boronic acid, pinacol boronate, and trifluoroborate salt. This method extends the realm of chemical reactions compatible with useful boron-containing substrates.


Synthesis, Characterization, Biomedical Application, Molecular Dynamic Simulation and Molecular Docking of Schiff Base Complex of Cu(II) Supported on Fe3O4/SiO2/APTS.
Over the past several years, nano-based therapeutics were an effective cancer drug candidate in order to overcome the persistence of deadliest diseases and prevalence of multiple drug resistance (MDR). The main objective of our program was to design organosilane-modified Fe3O4/SiO2/APTS(~NH2) core magnetic nanocomposites with functionalized copper-Schiff base complex through the use of (3-aminopropyl)triethoxysilane linker as chemotherapeutics to cancer cells. The nanoparticles were characterized by Fourier transform infrared spectroscopy (FT-IR), X-ray powder diffraction (XRD), field emission scanning electron microscopy (FE-SEM), TEM, and vibrating sample magnetometer (VSM) techniques. All analyses corroborated the successful synthesis of the nanoparticles. In the second step, all compounds of magnetic nanoparticles were validated as antitumor drugs through the conventional MTT assay against K562 (myelogenous leukemia cancer) and apoptosis study by Annexin V/PI and AO/EB. The molecular dynamic simulations of nanoparticles were further carried out; afterwards, the optimization was performed using MM+, semi-empirical (AM1) and Ab Initio (STO-3G), ForciteGemo Opt, Forcite Dynamics, Forcite Energy and CASTEP in Materials studio 2017. The results showed that the anti-cancer activity was barely reduced after modifying the surface of the Fe3O4/SiO2/APTS nanoparticles with 2-hydroxy-3-methoxybenzaldehyde as Schiff base and then Cu(II) complex. The apoptosis study by Annexin V/PI and AO/EB stained cell nuclei was performed that apoptosis percentage of the nanoparticles increased upon increasing the thickness of Fe3O4 shell on the magnetite core. The docking studies of the synthesized compounds were conducted towards the DNA and Topoisomerase II via AutoDock 1.5.6 (The Scripps Research Institute, La Jolla, CA, USA). Results of biology activities and computational modeling demonstrate that nanoparticles were targeted drug delivery system in cancer treatment.


Treatment-free remission in patients with chronic myeloid leukaemia.
In the past few years, international treatment guidelines for chronic myeloid leukaemia have incorporated recommendations for attempting discontinuation of treatment with tyrosine-kinase inhibitors (TKIs) outside of the setting of a clinical trial with the aim of a treatment-free remission (TFR). Physicians involved in the treatment of chronic myeloid leukaemia need to be sufficiently well informed to guide patients through decision-making about the discontinuation of treatment with TKIs targeting BCR-ABL1 by providing a balanced assessment of the potential risks and benefits of stopping or continuing therapy. These guidelines also seek to ensure that the risks associated with being off treatment are kept to a minimum. In this Review, we summarize the clinical studies of TFR and how their results can guide routine clinical practice with a focus on specific aspects such as molecular monitoring and the pregnancy-specific risks associated with a TFR attempt in female patients. We also address the development of predictors of outcome after TKI discontinuation and present strategies that warrant further consideration to enable more patients to enter TFR.


[Diuretic activity of the infusion of flowers from Lavandula officinalis].
The diuretic activity of an infusion of Lavandula officinalis was studied in the Wistar rat. Thus, the kinetics of hydroelectrolytic elimination in response to the oral administration of an infusion of pharmaceutical lavender flowers were measured in the rats. Experiments were completed under similar conditions using a synthetic pharmacological diuretic, Diamox. The aqueous extract of this aromatic plant accelerated the elimination of the water overload. At the peak of the diuretic response, urinary osmolarity was significantly less than that of controls (111+/-14 vs. 195+/-11 mosmol x kg(-1)). Sodium excretion was moderate following administration of the infusion when compared to the synthetic diuretic. The stability of the aldosterone concentrations in the plasma and the absence of correlation with plasma sodium concentrations, coupled with the observed clearance of the free water (0.055+/-0.007 vs. 0.045+/-0.012 mL x min(-1)) show that the increase in diuresis and the moderate increase in sodium excretion are of tubular origin. The result of the phytochemical analysis of hexane extracts in the infusion and in urine indicated that four or five chemical factors may be involved in the diuretic effect of lavender.


Provider-identified barriers and facilitators to implementing a supported employment program in spinal cord injury.
In a 5-year study, individual placement and support (IPS) significantly increased employment rate of United States Veterans with spinal cord injury (SCI), a historically underemployed population. In a follow-up study, data on barriers and facilitators to IPS implementation were identified. Over 24 months of implementation, 82 key medical and vocational staff underwent semi-structured interviews (n = 130). Interviews were digitally recorded and qualitatively analyzed (ATLAS.ti v0.7) using a constant comparative method to generate themes. Some barriers to implementation occurred throughout the study, such as Veterans' lack of motivation and providers' difficulty integrating vocational and medical rehabilitation. Other barriers emerged at specific stages, for example, early barriers included a large geographic service area and a large patient caseload, and late barriers included need for staff education. Facilitators were mostly constant throughout implementation and included leadership support and successful integration of vocational staff into the medical care team. Implementation strategies need to be adjusted as implementation progresses and matures. The strategies that succeeded in this setting, which were situated in a real-world context of providing IPS as a part of SCI medical care, may inform implementation of IPS for other populations with physical disabilities. Implications for Rehabilitation Key facilitators to IPS in SCI implementation are integrating vocational staff with expertise in IPS and SCI on clinical rehabilitation teams and providing leadership support. Ongoing barriers to IPS in SCI include patient specific and program administration factors such as caseload size and staffing patterns. Varying implementation strategies are needed to address barriers as they arise and facilitate successful implementation.


The concept of the alpha-amylase family: structural similarity and common catalytic mechanism.
This review reconsiders the concept of the alpha-amylase family in the light of the recent wealth of information on the structures, the catalytic mechanisms, and the classification of amylases. We proposed a general concept for an enzyme family, the alpha-amylase family including most of the amylases and related enzymes in 1992, based on the structural similarity and the common catalytic mechanisms. The study on neopullulanase was the key to open the door for the formulation of the concept. We discovered a new enzyme, neopullulanase, and proved that the enzyme catalyzes both hydrolysis and transglycosylation at alpha-1,4- and alpha-1,6-glucosidic linkages by one active center. Results from a series of experiments using neopullulanase indicated that the four reactions mentioned above could be catalyzed in the same mechanism. Progress in X-ray crystallographic analysis has allowed researchers to observe the structural similarities among alpha-amylases, cyclodextrin glucanotransferases, and an isoamylase. The primary structural analyses and the secondary structural predictions also suggest a close relationship among enzymes with three-dimensional structures which catalyze one of the four reactions. They possess a catalytic (beta/alpha)8-barrel as observed in the crystal structure of alpha-amylases, cyclodextrin glucanotransferases, and an isoamylase. Two crucial points, the common catalytic mechanisms and the structural similarities among the enzymes which catalyze the four reactions, led us to propose the concept of the alpha-amylase family. We would like to point out the significance and problems of the sequence-based classification of glycosyl hydrolases. The possible catalytic mechanism of the alpha-amylase family enzyme is also described for the rational design of tailor-made artificial enzymes.


Virtual reality: consumer perspectives.
This commentary extends the discussion of the applications of virtual reality to persons with disabilities by focusing on: (a) the use of virtual reality for stimulating residential features for persons being deinstitutionalized into four-person community residences; and (b) the involvement of consumers in key decisions regarding their residence and personal assistive technologies.